Using the isolated, perfused spleen of the cat and the isolated, perfused guinea-pig heart, studies on the regulation of neurotransmitter release and metabolism will be continued. The role of the putative alpha presynaptic receptor as a component of a negative feedback system for regulating nerve stimulated norepinephrine release will be examined further as will the role of cyclic nucleotides in exocytotic release. The mechanism by which reserpine-like agents enhance exocytotic release of norepinephrine and dopamine-beta-hydroxylase will be investigated and the particular role of norepinephrine and its deaminated metabolites in regulating the release process will be evaluated. The synthesis and turnover of storage vesicle adenine necleotides and the effect of nerve stimulation on the synthesis, release and turnover of this component of the storage vesicle will be determined. Pharmacological interactions between adenine nucleotides and catecholamines will be studied in the isolated perfused spleen. A systematic analysis of the factors which significantly influence the maintenance of neurotransmitter stores during and after prolonged stimulation of the nerve to the isolated perfused spleen will be made. The role of transaminases and gamma keto acids in regulating tyrosine and dopa metabolism and norepinephrine syntheis in brain and in peripheral adrenergic nervous tissue will be pursued further. The mechanisms by which amphetamine modifies tyrosine hydroxylase activity in intact, isolated tissues will be investigated further.